Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP

• Published in: Journal of cerebral blood flow and metabolism 2016-01, Vol.36 (1), p.241-252
• Main Authors: Faraco, Giuseppe, Park, Laibaik, Zhou, Ping, Luo, Wenjie, Paul, Steven M, Anrather, Josef, Iadecola, Costantino
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - pharmacology; Amyloid beta-Protein Precursor - blood; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases - metabolism; Angiotensin II - pharmacology; Animals; Blood Pressure - drug effects; Cerebral Amyloid Angiopathy - etiology; Cerebral Amyloid Angiopathy - metabolism; Cerebral Amyloid Angiopathy - pathology; Cerebrovascular Circulation - drug effects; CHO Cells; Cricetulus; Disease Models, Animal; Hypertension - complications; Hypertension - metabolism; Hypertension - pathology; Male; Mice, Inbred C57BL; Mice, Transgenic; Original
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2015.79

Hypertension (HTN) doubles the risk of Alzheimer’s disease (AD), but the mechanisms remain unclear. Amyloid-β (Aβ), a key pathogenic factor in AD, induces cerebrovascular dysfunction. We hypothesized that HTN acts in concert with Aβ to amplify its deleterious cerebrovascular effects and to increase Aβ production. Infusion of angiotensin II (ANGII; intravenously) elevated blood pressure and attenuated the cerebral blood flow (CBF) response to whisker stimulation or the endothelium-dependent vasodilator acetylcholine (ACh) (P